The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference.
Testicular descent occurs in two steps on the embryonic stage and the process is affected by several factors. Transabdominal descent begins after sexual differentiation at 8 to 10 weeks. The testis reaches the inguinal region at about the 15th week. The inguinal phase of testicular descent begins at 24-28 weeks when the testis rapidly passes through the inguinal canal and then more slowly arrives in the scrotum at 35-40 weeks (1).
The incidence of non-descended testis (in the following also called cryptorchidism, which term stands for failure of one or both of the testes to descend) has been 4.3% in all newborn male infants. At the age of three months the incidence is 1.0% and at the age of one year 0.8%. According to a recent English study, the incidence of non-descended testis has risen to 5.1% among newborns and 1.6% at the age of three months (2). Also in Denmark a growth of the incidence has been reported. Some of the increase may be attributed to the increased viability of very low birth weight infants, but even in full-term infants the incidence has risen to 4.1% at birth and 1.6% at three months (2). Excessive maternal exposure to estrogens such as diethylstilbestrol and to oral contraceptives has been suggested as an etiological factor associated with the increased incidence of cryptorchidism. Endogenous estrogens have also been suggested to be relevant to testicular non-descent. An increased risk of cryptorchidism and testicular cancer has been associated with elevated maternal estrogen consentrations during pregnancy (3). Overweight women that are nulliparous have lower SHBG levels, with a resulting higher bioavailability for estrogens. The increase in the amount of biologically active estrogens may extend during pregnancy and subsequently lead to a clinical condition that exposes the fetus to high estrogen levels (3). There is experimental evidence confirming the role of estrogens. Perinatal exposure of the mouse to either 17β-estradiol or diethylstilbestrol results in testicular abnormalities such as cryptorchidism, testicular hypoplasia, sperm abnormalities, epididymal cysts and testicular tumors (4 and 5).
Testicular maldescent may strongly influence male fertility even when treated and fertility is frequently impaired, particularly in cases of bilateral cryptorchidism. Testicular cancer is also associated with cryptorchidism.
One method for the treatment of cryptorchidism is surgery. Some decades ago, the surgery was carried out at the age of about 5-10 years. There has, however, been a stepwise decrease in the age at which surgery should be carried out, mainly due to histological evidence of testicular damage which occurs in untreated non-descended testis after infancy. At present, the operation is recommended before two years age.
Cryptorchidism has also be subjected to hormonal treatment with hCG (human chorionic gonadotrophin) or LHRH (lutenizing-hormone releasing hormone). During the last decades the success rate of hCG treatment has varied from 6 to 55%. The success rates achieved by using LHRH have been reported to vary between 9 and 78%. According to one study, both LHRH and hCG have been found to be ineffective in cases of true non-descended testes.
The known treatment methods are also related to risks. The most significant complication of surgery is vascular damage. Hormonal treatment may also have adverse effects on the testis. Inflammation-like reactions have been found in non-descended testes during the period immediately following hCG injections.
Thus, there is a great need for improved treatment methods of cryptorchidism.